1. Field of the Invention
The present invention relates to a method for producing a patch, a patch and a package. More specifically, the present invention relates to a method for producing a patch using ropinirole as a drug and a patch and a package obtained by the method.
2. Related Background Art
Conventionally, the oral administration method using a tablet, a capsule, a syrup, or the like has been known as a drug administration method. In recent years, the transdermal administration method has been studied in which a drug is transdermally administered by using a patch. The method using a patch can solve problems associated with the oral administration method, and has advantages such as reduction in frequency of administration, improvement in compliance, and ease of administration and discontinuation. For these reasons, the transdermal administration method is expected as a drug administration method useful especially in a case of elderly or child patients.
The stratum corneum of the normal skin has a barrier function of preventing foreign substances from entering the body. Because of the barrier function, the use of conventional patches often ends up with insufficient transdermal absorption of the formulated drug ingredient. Moreover, since the stratum corneum is highly lipophilic, the skin penetrability of a drug is extremely low, in general.
In a generally known method for enhancing the skin penetrability of a drug in the transdermal administration method, the drug is contained at a supersaturated concentration in a transdermal preparation, and the difference in concentration gradient of the drug is utilized, as described in “Pharmaceutical Skin Penetration Enhancement,” edited by K A Walters and J Hadgraft, (the United States), Vol. 59, Marcel Dekker, 1993, pp. 243-267. For example, Japanese Patent Application Publication No. Sho 63-93714 (Patent Literature 1) describes a patch comprising an adhesive agent layer containing a drug at a supersaturated concentration. However, the method in which a drug is contained at a supersaturated concentration in an adhesive agent layer of a patch involves an increased possibility of crystal precipitation of the drug. Hence, the method has problems associated with the crystal precipitation, such as reduction in cohesiveness and adhesion of the adhesive agent layer and reduction in skin penetrability due to a reduced drug release rate. Furthermore, Patent Literature 1 describes melting of crystals of the drug precipitated during storage by heating before use. However, such a method requires the heating operation every time the patch is used, and hence has problems in terms of convenience and ease of administration.
Moreover, studies have been recently made on transdermal administration of pharmaceutical preparations containing ropinirole, which is a drug useful for treating Parkinson's disease, restless legs syndrome, etc. and/or pharmaceutically acceptable salts thereof. For example, International Application Japanese-Phase Publication No. 2009-518376 (Patent Document 2) lists ropinirole as a drug contained in a composition for local administration. International Application Japanese-Phase Publication No. 2001-518058 (Patent Document 3) and International Application Japanese-Phase Publication No. Hei 11-506462 (Patent Document 4) disclose a transdermal pharmaceutical preparation comprising a support layer and a layer containing ropinirole. However, each of the patches described in Patent Documents 2 to 4 has such a problem that the skin penetrability of ropinirole is still insufficient, and hence it is difficult to keep the plasma concentration of ropinirole at a sufficiently high level. Moreover, each of the patches described in Patent Documents 2 to 4 has a problem of insufficient stability over time of ropinirole.
In addition, as a patch having excellent skin penetrability and stability of ropinirole, for example, International Publication No. WO 2009/107478 (Patent Document 5) describes a patch in which an adhesive agent layer contains free ropinirole formed by a reaction of an acid addition salt of ropinirole with a metal-ion containing desalting agent. International Publication No. WO 2012/165253 (Patent Document 6) describes a patch in which an adhesive agent layer contains a specific amount of ropinirole and/or a pharmaceutically acceptable salt thereof.